Application | Comment | Organism |
---|---|---|
medicine | REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug | Staphylococcus aureus |
medicine | REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug | Haemophilus influenzae |
medicine | REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug | Escherichia coli |
medicine | REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug | Homo sapiens |
medicine | REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug | Streptococcus pneumoniae |
medicine | REP3123 represents a promising narrow spectrum, new mode-of-action agent with an excellent microbiological profile that warrants its further evaluation as a novel drug to combat Clostridium difficile infections | Clostridioides difficile |
Cloned (Comment) | Organism |
---|---|
full-length MetRS with an N-terminal His-tag is overexpressed in Escherichia coli | Clostridioides difficile |
Protein Variants | Comment | Organism |
---|---|---|
D229E | spontaneous resistant mutant, first step | Clostridioides difficile |
D229N | serial passage mutant | Clostridioides difficile |
D229N | spontaneous resistant mutant, first step | Clostridioides difficile |
G213C | spontaneous resistant mutant, first step | Clostridioides difficile |
G213D | spontaneous resistant mutant, first step | Clostridioides difficile |
G54A | spontaneous resistant mutant, first step | Clostridioides difficile |
G54C | spontaneous resistant mutant, first step | Clostridioides difficile |
G54S | spontaneous resistant mutant, first step | Clostridioides difficile |
G54S/L203S | spontaneous resistant mutant, second step | Clostridioides difficile |
H101D | spontaneous resistant mutant, first step | Clostridioides difficile |
H101L | spontaneous resistant mutant, first step | Clostridioides difficile |
H101N | spontaneous resistant mutant, first step | Clostridioides difficile |
H101N/G213C | spontaneous resistant mutant, second step | Clostridioides difficile |
I105M/G213D | spontaneous resistant mutant, second step | Clostridioides difficile |
I57N | spontaneous resistant mutant, first step | Clostridioides difficile |
I57N/H101N | spontaneous resistant mutant, second step | Clostridioides difficile |
T236K | spontaneous resistant mutant, first step | Clostridioides difficile |
V216A | spontaneous resistant mutant, first step | Clostridioides difficile |
V216F/L203S | spontaneous resistant mutant, second step | Clostridioides difficile |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
REP3123 | active against a collection of 108 clinical isolates of Clostridium difficile and against epidemic, moxifloxacin-resistant BI/NAP1/027 strains | Clostridioides difficile | |
REP3123 | - |
Escherichia coli | |
REP3123 | - |
Haemophilus influenzae | |
REP3123 | - |
Homo sapiens | |
REP3123 | - |
Staphylococcus aureus | |
REP3123 | - |
Streptococcus pneumoniae |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00055 | - |
tRNAMet | wild-type, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.00064 | - |
tRNAMet | mutant G54S/L203S, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.00065 | - |
tRNAMet | mutant D229E, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.0008 | - |
tRNAMet | mutant V216A, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.00096 | - |
tRNAMet | mutant V216F/L203S, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.00102 | - |
tRNAMet | mutant G54S, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.00121 | - |
tRNAMet | mutant I57N/H101N, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.0026 | - |
tRNAMet | mutant I57N, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.006 | - |
L-methionine | mutant I57N, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.017 | - |
L-methionine | mutant V216A, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.025 | - |
L-methionine | mutant V216F/L203S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.025 | - |
L-methionine | wild-type, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.055 | - |
L-methionine | mutant G54S/L203S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.092 | - |
L-methionine | mutant D229E, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.16 | - |
L-methionine | mutant G54S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.19 | - |
L-methionine | mutant I57N/H101N, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.375 | - |
ATP | wild-type, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.44 | - |
ATP | mutant G54S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.475 | - |
ATP | mutant H101N/G213C, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.7 | - |
ATP | mutant H101D, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.78 | - |
ATP | mutant V216A, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.85 | - |
ATP | mutant V216F/L203S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
0.98 | - |
ATP | mutant D229E, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
1 | - |
ATP | mutant I57N, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
1.35 | - |
ATP | mutant G54S/L203S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
1.55 | - |
L-methionine | mutant H101N/G213C, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
1.75 | - |
ATP | mutant I57N/H101N, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
14.8 | - |
L-methionine | mutant H101D, first step of reaction, methionyl-adenylate formation | Clostridioides difficile |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytoplasm | - |
Homo sapiens | 5737 | - |
mitochondrion | - |
Homo sapiens | 5739 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-methionine + tRNAMet | Staphylococcus aureus | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Haemophilus influenzae | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Escherichia coli | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Homo sapiens | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Streptococcus pneumoniae | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | Clostridioides difficile | - |
AMP + diphosphate + L-methionyl-tRNAMet | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Clostridioides difficile | - |
- |
- |
Escherichia coli | - |
- |
- |
Haemophilus influenzae | - |
- |
- |
Homo sapiens | - |
- |
- |
Staphylococcus aureus | - |
- |
- |
Streptococcus pneumoniae | - |
- |
- |
Purification (Comment) | Organism |
---|---|
using Ni-affinity and SourceQ anion exchange chromatography | Clostridioides difficile |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-methionine + tRNAMet | - |
Staphylococcus aureus | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Haemophilus influenzae | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Escherichia coli | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Homo sapiens | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Streptococcus pneumoniae | AMP + diphosphate + L-methionyl-tRNAMet | - |
? | |
ATP + L-methionine + tRNAMet | - |
Clostridioides difficile | AMP + diphosphate + L-methionyl-tRNAMet | - |
? |
Synonyms | Comment | Organism |
---|---|---|
methionyl-tRNA synthetase | - |
Staphylococcus aureus |
methionyl-tRNA synthetase | - |
Haemophilus influenzae |
methionyl-tRNA synthetase | - |
Escherichia coli |
methionyl-tRNA synthetase | - |
Homo sapiens |
methionyl-tRNA synthetase | - |
Streptococcus pneumoniae |
methionyl-tRNA synthetase | - |
Clostridioides difficile |
MetRS | - |
Staphylococcus aureus |
MetRS | - |
Haemophilus influenzae |
MetRS | - |
Escherichia coli |
MetRS | - |
Homo sapiens |
MetRS | - |
Streptococcus pneumoniae |
MetRS | - |
Clostridioides difficile |
MetRS1 | - |
Streptococcus pneumoniae |
MetRS2 | - |
Streptococcus pneumoniae |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.006 | - |
tRNAMet | mutant V216F/L203S, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.01 | - |
tRNAMet | mutant G54S, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.011 | - |
tRNAMet | mutant G54S/L203S, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.013 | - |
tRNAMet | mutant I57N/H101N, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.017 | - |
tRNAMet | mutant I57N, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.023 | - |
tRNAMet | mutant D229E, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.055 | - |
tRNAMet | mutant V216A, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
0.08 | - |
tRNAMet | wild-type, second step of reaction, tRNA aminoacylation | Clostridioides difficile | |
4 | - |
L-methionine | mutant G54S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
6 | - |
L-methionine | mutant I57N/H101N, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
8 | - |
L-methionine | mutant H101N/G213C, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
15 | - |
L-methionine | mutant G54S/L203S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
15 | - |
L-methionine | mutant H101D, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
15 | - |
L-methionine | mutant I57N, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
23 | - |
L-methionine | wild-type, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
25 | - |
L-methionine | mutant V216A, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
25 | - |
L-methionine | mutant V216F/L203S, first step of reaction, methionyl-adenylate formation | Clostridioides difficile | |
33 | - |
L-methionine | mutant D229E, first step of reaction, methionyl-adenylate formation | Clostridioides difficile |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Staphylococcus aureus | |
ATP | - |
Haemophilus influenzae | |
ATP | - |
Escherichia coli | |
ATP | - |
Homo sapiens | |
ATP | - |
Streptococcus pneumoniae | |
ATP | - |
Clostridioides difficile |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.000000017 | - |
REP3123 | - |
Staphylococcus aureus | |
0.00000002 | - |
REP3123 | wild-type | Clostridioides difficile | |
0.00000008 | - |
REP3123 | MetRS1 | Streptococcus pneumoniae | |
0.0000002 | - |
REP3123 | mutant I57N | Clostridioides difficile | |
0.00001 | - |
REP3123 | mutant V216F/L203S | Clostridioides difficile | |
0.000013 | - |
REP3123 | mutant G54S | Clostridioides difficile | |
0.000018 | - |
REP3123 | mutant D229E | Clostridioides difficile | |
0.000028 | - |
REP3123 | mitochondrial MetRS | Homo sapiens | |
0.00007 | - |
REP3123 | mutant V216A | Clostridioides difficile | |
0.000155 | - |
REP3123 | mutant I57N/H101N | Clostridioides difficile | |
0.000178 | - |
REP3123 | - |
Haemophilus influenzae | |
0.000375 | - |
REP3123 | mutant H101D | Clostridioides difficile | |
0.0005 | - |
REP3123 | mutant G54S/L203S | Clostridioides difficile | |
0.001 | - |
REP3123 | mutant H101N/G213C | Clostridioides difficile | |
0.0019 | - |
REP3123 | - |
Escherichia coli | |
0.02 | - |
REP3123 | cytoplasmic MetRS | Homo sapiens | |
0.02 | - |
REP3123 | MetRS2 | Streptococcus pneumoniae |